Effects of Transglutaminase 2 Inhibition on Ventilator-Induced Lung Injury

This study was performed to examine the role of transglutaminase 2 (TG2) in ventilator-induced lung injury (VILI). C57BL/6 mice were divided into six experimental groups: 1) control group; 2) lipopolysaccharide (LPS) group; 3) lung protective ventilation (LPV) group; 4) VILI group; 5) VILI with cystamine, a TG2 inhibitor, pretreatment (Cyst+VILI) group; and 6) LPV with cystamine pretreatment (Cyst+LPV) group. Acute lung injury (ALI) score, TG2 activity and gene expression, inflammatory cytokines, and nuclear factor-κB (NF-κB) activity were measured. TG2 activity and gene expression were significantly increased in the VILI group (P < 0.05). Cystamine pretreatment significantly decreased TG2 activity and gene expression in the Cyst+VILI group (P < 0.05). Inflammatory cytokines were higher in the VILI group than in the LPS and LPV groups (P < 0.05), and significantly lower in the Cyst+VILI group than the VILI group (P < 0.05). NF-κB activity was increased in the VILI group compared with the LPS and LPV groups (P < 0.05), and significantly decreased in the Cyst+VILI group compared to the VILI group (P = 0.029). The ALI score of the Cyst+VILI group was lower than the VILI group, but the difference was not statistically significant (P = 0.105). These results suggest potential roles of TG2 in the pathogenesis of VILI.

Graphical Abstract

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The alpha-lipoic acid derivative DHLHZn: a new therapeutic agent for acute lung injury in vivo

Objective and design

An animal experiment was performed to demonstrate the anti-inflammatory effects of an alpha-lipoic acid (ALA) derivative, dihydrolipoyl histidinate zinc complex (DHLHZn) for acute lung injury (ALI) and to investigate the mechanism of action.

Material

Rats were randomly divided into three experimental groups: control group (n = 17), DHLHZn(?) group (n = 11, ALI model rats), and DHLHZn(+) group (n = 12, ALI model rats treated by DHLHZn).

Treatment

Lipopolysaccharides (LPS, 10 mg/kg) were administered intratracheally in the DHLHZn(?) group and the DHLHZn(+) group. For the DHLHZn(+) group, DHLHZn (100 mg/kg) was administered intraperitoneally 2 h prior to LPS administration.

Methods

Four hours after LPS administration, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings were analyzed using the Mann–Whitney U test.

Results

Total number of cells, number of neutrophils and lymphocytes, levels of various inflammatory cytokines, and NF-kB p65 concentration of BALF were significantly lower in the DHLHZn(+) group than in the DHLHZn(?) group (p < 0.05). ALI pathology scores were significantly lower in the DHLHZn(+) group than in the DHLHZn(?) group (p < 0.001).

Conclusions

Anti-inflammatory effects of DHLHZn for ALI were demonstrated by BALF and histopathological findings. The mechanism of action of DHLHZn was considered to be via inhibition of the NF-kB signaling pathway. DHLHZn is thus suggested to be a new prophylactic agent for ALI.

     

KGFR promotes Na+ channel expression in a rat acute lung injury model

Background

Binding of keratinocyte growth factor (KGF) to the KGF receptor (KGFR) plays an important role in the recovery of alveolar epithelial cells from acute lung injury (ALI).

Objectives

To evaluate the effect of gene therapy via adenovirus gene transfer of KGFR on the treatment of ALI.

Methods

Sprague-Dawley rats were divided into four groups: normal controls, injury controls, normal adenovirus transduced group and injury adenovirus transduced group. The ALI model was induced by lipopolysaccharide (LPS) injection. Recombinant adenovirus (AdEasy-KGFR) was injected via the tail vein. Expression of the sodium (Na⁺) channel in rat alveolar type II (ATII) epithelial cells was determined by PCR, immunohistochemistry and immunoelectron microscopy of rat lung tissues.

Results

Gene expression of the Na⁺ channel and KGFR in ATII cells was higher in the normal adenovirus transduced group than the three other groups; expression of these two genes in the injury adenovirus transduced group was higher than the injury control group. Na⁺ channel protein expression was lower in the injury adenovirus transduced group but higher than the injury control group.

Conclusions

KGFR over-expression induced Na channel expression could potentially be beneficial for ALI therapy.     

Ozone preconditioning and exposure to ketamine attenuates hepatic inflammation in septic rats

Introduction

The objective of this study was to evaluate the interaction between ozone oxidative preconditioning and the anesthetic ketamine on cytoplasmic nuclear factor κB (NF-κB) levels in a rat endotoxic shock model.

Material and methods

Forty Wistar rats were randomly divided into 5 groups: I – control group; II – rats intraperitoneally (i.p.) treated with LPS; III – rats treated with LPS and then treated with ketamine; IV – animals pre-treated with O₃/O₂ mixture for 5 days, then treated with LPS for 24 h followed by infusion with ketamine; V – O₃/O₂ pre-treatment, as described above for IV, followed by LPS infusion, and then 0.9% saline. In addition to histological examination of the liver, the levels of NF-κB were determined by SABC immunohistochemistry in each group.

Results

Histological damage was observed in the lipopolysaccharide (LPS) group. It was characterized by hepatic disarray, hepatic lobule distortion, congestion of liver sinusoids, hepatocyte swelling and necrosis, and granulocyte infiltration. These changes were not obvious in the O₃/O₂ + LPS + ketamine group. The normal control group had low activity of NF-κB, but that activity was markedly increased in the LPS group (p < 0.05). The NF-κB level was significantly decreased in the O₃/O₂ + LPS + ketamine group (p < 0.05) when compared with the ketamine-treated group, and was almost equal to the control group.

Conclusions

We confirmed that the preconditioning effect of ozone enhances the biological effectiveness of ketamine by altering NF-κB activity, which may play an important role in sepsis-induced liver injury in rats.     

Expression of pulmonary aquaporin 1 is dramatically upregulated in mice with pulmonary fibrosis induced by bleomycin

Introduction

Pulmonary fibrosis occurs due to fibroblast proliferation and collagen production in the lung and begins with alveolar inflammatory edema. Aquaporins (AQPs) play pivotal roles in lung fluid transport. In this study we establish the experimental model for pulmonary fibrosis in C57BL/6 mice to investigate expressions of AQP1 and AQP5 in lung tissue.

Material and methods

Mice in model groups were treated intratracheally with bleomycin with the dose of 5 mg/kg body weight. The mice were sacrificed at 1 week, 2 weeks and 3 weeks respectively. The left upper lungs were harvested for histopathologic H-E and Masson''s staining. The mRNAs of AQP1 and AQP5 were analyzed by real-time polymerase chain reaction (real-time PCR) and the proteins of AQP1 and AQP5 were analyzed by western blotting.

Results

Real-time PCR showed that AQP1 mRNA in bleomycin 1 w, 2 w, and 3 w groups increased by 377%, 880% and 823% respectively compared to that in the control group (p < 0.01). Western blotting showed that the expression of AQP1 protein in bleomycin 1 w, 2 w, and 3 w groups increased by 53%, 144%, and 141%, respectively (p < 0.05). AQP5 mRNA in bleomycin 1 w and 2 w group decreased by 78% and 66%, respectively (p < 0.05). In bleomycin 2 w and 3 w groups it decreased by 69% and 80% (p < 0.05).

Conclusions

The expression of AQP1 dramatically increased in pulmonary fibrosis. AQP1 plays an important role in the progress of pulmonary fibrosis.     

Cystathionine-gamma-lyase inhibitor attenuates acute lung injury induced by acute pancreatitis in rats

Introduction

Acute pancreatitis (AP) is known to induce injuries to extrapancreatic organs. Because respiratory dysfunction is the main cause of death in patients with severe AP, acute pancreatitis-associated lung injury (APALI) is a great challenge for clinicians. This study aimed to investigate the potential role of hydrogen sulfide (H₂S) in the pathogenesis of APALI.

Material and methods

Fifty-four SD rats were randomly divided into three groups: the AP group of rats that received injection of sodium deoxycholate into the common bile duct, the control group that underwent a sham operation, and the treatment group made by intraperitoneal injection of propargylglycine (PAG), an inhibitor of cystathionine-γ-lyase (CSE), into rats with AP. Histopathology of the lung was examined and the expression of CSE and TNF-α mRNA in lung tissue was detected by real-time polymerase chain reaction. The H₂S level in the serum was detected spectrophotometrically.

Results

The serum concentration of H2S and CSE and TNF-α expression in the lung were increased in AP rats modeled after 3 h and 6 h than in control rats (p < 0.05). Intraperitoneal injection of PAG could reduce the serum concentration of H₂S, reduce CSE and TNF-α expression, and alleviate the lung pathology (p < 0.05).

Conclusions

Taken together, our findings suggest that the H₂S/CSE system is crucially involved in the pathological process of APALI and represents a novel target for the therapy of APALI.     

Detection and significance of TregFoxP3+ and Th17 cells in peripheral blood of non-small cell lung cancer patients

Introduction

The aim of this study was to explore the relationships between TregFoxP3⁺ cells and Th17 cells and occurrence of lung cancer.

Material and methods

The proportions of TregFoxP3⁺ and Th17 cells, the expression of FoxP3 and RORγt mRNA, and the levels of related cell factors such as transforming growth factor-β (TGF-β), interleukin IL-17 (IL-17) and IL-23 were determined respectively by flow cytometry analysis, real-time-polymerase chain reaction (PCR), and ELISA in peripheral blood of 18 healthy people and 26 patients with non-small cell lung cancer (NSCLC).

Results

The levels of TregFoxP3⁺ and Th17, expression of FoxP3 and RORγt mRNA, and ratios of TregFoxP3⁺/Th17 and FoxP3/RORγt in peripheral blood with NSCLC were higher than those in healthy controls (p < 0.05). The proportion of Th17 cells from NSCLC patients was positively correlated with that of TregFoxP3⁺ (r = 0.81, p < 0.05). The receiver-operating characteristic (ROC) curve demonstrates that the increased level of TregFoxP3⁺/Th17 in the peripheral blood may be a useful indicator in early diagnosis of non-small cell lung carcinoma. The TregFoxP3⁺/Th17 and FoxP3/RORγt levels for patients in stage IV were higher than those of patients in stages I, II, and III (p < 0.05). The levels of TGF-β, IL-17, and IL-23 were higher in NSCLC patients than those in healthy controls.

Conclusions

The results suggest that ratios of Treg/Th17 correlate with the stage of NSCLC.     

Cavidine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury <Emphasis Type="Italic">via</Emphasis> NF-κB Signaling Pathway <Emphasis Type="Italic">in vivo</Emphasis> and <Emphasis Type="Italic">in vitro</Emphasis>

Acute lung injury (ALI) is characterized by widespread inflammation in the lungs and alveolar-capillary destruction, causing high morbidity and mortality. Cavidine, isolated from Corydalis impatiens, have been exhibited to have potent anti-inflammatory effects in previous studies. The purpose of this study was to evaluate the protective effect of cavidine on lipopolysaccharide (LPS)-induced ALI and to enunciate the underlying in vivo and in vitro mechanisms. Mice were intraperitoneally administrated with cavidine (1, 3, or 10 mg/kg) at 1 and 12 h, prior to the induction of ALI by intranasal administration of LPS (30 mg/kg). Blood samples, lung tissues, and bronchoalveolar lavage fluid (BALF) were harvested after LPS challenge. Furthermore, we used LPS-induced lung epithelial cells A549 to examine the mechanism of cavidine to lung injury. The results showed that pretreatment with cavidine significantly decreased lung wet-to-dry weight (W/D) ratio, reduced pro-inflammatory cytokine levels including TNF-α and IL-6 in BALF and serum from LPS-stimulated mice, and attenuated lung histopathological changes. In addition, western blot results showed that cavidine inhibited the phosphorylation of nuclear factor-kappaB (NF-κB) p65 and IκBα induced by LPS. In conclusion, our results demonstrate that cavidine protects against LPS-induced acute lung injury in mice via inhibiting of pro-inflammatory cytokine TNF-α and IL-6 production and NF-κB signaling pathway activation. Taken together, cavidine may be useful for the prevention and treatment of pulmonary inflammatory diseases, such as ALI.     

Hyponatremia in critically ill patients

Context:

Hyponatremia is a common electrolyte disturbance in critically ill hence understanding its implications is important.

Aims:

This study was carried out to ascertain frequency, predisposing conditions and outcome in critically ill patients with hyponatremia on intensive care unit (ICU) admission.

Settings and Design:

This was an observational, prospective study of a series of ICU patients during a 12-month period.

Materials and Methods:

The patients were divided into two groups: Hyponatremic (serum sodium < 135 mmol/L) and Eunatremic groups (135-145 mmol/L). Clinical examination included volume status and drug history, biochemistries, clinical diagnosis and cause of hyponatremia.

Statistical Analysis Used:

Fisher''s exact test, unpaired t-tests Wilcoxon ranksum tests, profile-likelihood method, log-rank test and Kaplan—Meier curves were used. P < 0.05 were considered to be statistically significant.

Results:

In the hyponatremic group, the frequency of hyponatremia on ICU admission was 34.3%, most were euvolumic, 58.96%. Females comprised of 36.5%. The mean age was 60.4 ± 17.2. The Syndrome of inappropriate Antidiuretic Hormone (SIADH) criteria was met in ninety-one patients (36.25%), peumonia being the leading cause of SIADH. Patients with severe sepsis, elective surgery patients, renal failure and heart failure, cirrhosis of liver and subarachnoid hemorrhage were other more likely etiologic causes (P < 0.05). The hyponatremic group spent a longer time in the ICU (P = 0.02), had longer mechanical ventilator days (P < 0.05) and had an increased mortality rate (P = 0.01).

Conclusions:

Hyponatremia present on admission to the ICU is independent risk factors for poor prognosis.     

Aberrant expression of cytokine interleukin 9 along with interleukin 4 and interferon γ in connective tissue disease-associated interstitial lung disease: association with severity of pulmonary fibrosis

Introduction

Connective tissues diseases (CTDs) are a heterogeneous group of disorders that share certain clinical characteristics and disturbed immunoregulation. Interstitial lung diseases (ILDs), also known as diffuse parenchymal lung diseases, are among the most serious pulmonary complications associated with CTDs. Interleukin 9 (IL-9), IL-4 and interferon γ (IFN-γ) – cytokines with important roles in autoimmune disease – were studied in CTD patients and CTD-ILD patients.

Material and methods

Sixty-one hospitalized untreated CTD patients were recruited, and 20 healthy volunteers were enrolled as controls. The 61 CTD patients were divided into a simple CTD group and a CTD-ILD group, and the plasma protein IL-9, IL-4 and IFN-γ levels were measured by enzyme-linked immunosorbent assay (ELISA).

Results

The results indicate that the serum IL-9 levels were significantly higher in CTD-ILD and simple CTD patients than they were in healthy controls (each p < 0.05) and that the levels were elevated in CTD-ILD patients compared with simple CTD patients (p < 0.05). The IL-4 levels were higher in CTD-ILD patients than they were in the simple CTD patients (p < 0.05) and healthy controls (p < 0.01). In addition, the serum IL-9 levels were negatively correlated with the level of IFN-γ (r² = 0.34, p = 0.01), the estimated percentage of predicted forced vital capacity (FVC%) (r² = 0.36, p = 0.00) and the estimated percentage of predicted diffusing capacity (DLCO%) (r² = 0.27, p = 0.04) and were positively correlated with the IL-4 level (r² = 0.31, p = 0.01).

Conclusions

Interleukin-9 may play an important role in the pathogenesis of CTD and may contribute to the progression of interstitial lung injury in CTD patients.     

Risk factors for hospital-acquired hypernatremia among critically ill medical patients in a setting utilizing a preventive free water protocol: Do we need to do more?

Context:

Hospital-acquired hypernatremia (HAH) is a frequent concern in critical care, which carries high mortality.

Aims:

To study the risk factors for HAH in settings that practice a preventive protocol.

Settings and Design:

Two tertiary-care hospitals. Prospective observational study design.

Materials and Methods:

Patients aged >18 years admitted for an acute medical illness with normal serum sodium and need for intensive care >48 h formed the study population. Details of the basic panel of investigations on admission, daily electrolytes and renal function test, sodium content of all intake, free water intake (oral, enteral and intravenous) and fluid balance every 24 h were recorded. Individuals with serum Na 140-142 meq/l received 500 ml of free water every 24 h, and those with 143-145 meq/l received 1000 ml free water every 24 h.

Statistical Analysis Used:

Risk factors associated with HAH was analysed by multiple logistic regression.

Results:

Among 670 study participants, 64 (9.5%) developed HAH. The median duration of hypernatremia was 3 days. A total 60 of 64 participants with HAH had features of renal concentrating defect during hypernatremia. Age >60 years (P = 0.02), acute kidney injury (AKI) on admission (P = 0.01), mechanical ventilation (P = 0.01), need for ionotropes (P = 0.03), worsening Sequential Organ Failure Assessment (SOFA) score after admission (P < 0.001), enteral tube feeds (P = 0.002), negative fluid balance (P = 0.02) and mannitol use (P < 0.001) were the risk factors for HAH. Mortality rate was 34.3% among hypernatremic patients.

Conclusions:

The study suggests that administration of free water to prevent HAH should be more meticulously complied with in patients who are elderly, present with AKI, suffer multi-organ dysfunction, require mechanical ventilation, receive enteral feeds and drugs like mannitol or ionotropes.     

The protective effects of Ambroxol in Pseudomonas aeruginosa-induced pneumonia in rats

Introduction

To evaluate the effect of Ambroxol on the pulmonary surfactant (PS) in rat pneumonia induced by Pseudomonas aeruginosa (PA).

Material and methods

The pneumonic rats were obtained by injecting ATCC27853 intratracheally. One hundred and twenty SD rats were randomized into four groups: normal saline and Ambroxol was injected intraperitoneally following PA challenge in the PA/NS and PA/AM group; the other two groups were NS/AM and NS/NS. The wet/dry weight ratio (W/D), and pathological changes were assayed. Total proteins (TP), total phospholipid (TPL), and dipalmitoylphosphatidylcholine (DPPC) in bronchial alveolar lavage fluid (BALF) were analysed. Some BALF was cultured for colony counts. Ultrastructural change of the lung was observed by electron microscopy.

Results

The W/D ratio in the PA/AM group was lower than that in the PA/NS group; both were higher than that in the NS/NS group (p < 0.05). There were more neutrophils in the PA/NS group than in the PA/AM group (p < 0.05), and more in the PA/AM group than in the NS/NS group (p < 0.05). The ratio of DSPC/TPL and DSPC/TP in the BALF in PA/NS group was lower than that in the PA/AM group; DSPC/TPL and DSPC/TP ratios also increased in the NS/AM group. The PA colony numbers in the PA/AM group were lower than in the PA/NS group (p > 0.05). In the PA/NS group, vacuolation occurred in the lamellar body of alveolar type 2 cells (AT2) and the PS layer was rough and broken in some areas. In the PA/AM group, the degree of vacuolation of the lamellar body was less than in the PA/NS group.

Conclusions

Ambroxol could protect rats from pneumonia by improving the level of endogenous PS, especially DPPC.     

Correlation between central venous pressure and peripheral venous pressure with passive leg raise in patients on mechanical ventilation

Background:

Central venous pressure (CVP) assesses the volume status of patients. However, this technique is not without complications. We, therefore, measured peripheral venous pressure (PVP) to see whether it can replace CVP.

Aims:

To evaluate the correlation and agreement between CVP and PVP after passive leg raise (PLR) in critically ill patients on mechanical ventilation.

Setting and Design:

Prospective observational study in Intensive Care Unit.

Methods:

Fifty critically ill patients on mechanical ventilation were included in the study. CVP and PVP measurements were taken using a water column manometer. Measurements were taken in the supine position and subsequently after a PLR of 45°.

Statistical Analysis:

Pearson''s correlation and Bland–Altman''s analysis.

Results:

This study showed a fair correlation between CVP and PVP after a PLR of 45° (correlation coefficient, r = 0.479; P = 0.0004) when the CVP was <10 cmH₂O. However, the correlation was good when the CVP was >10 cmH₂O. Bland–Altman analysis showed 95% limits of agreement to be −2.912–9.472.

Conclusion:

PVP can replace CVP for guiding fluid therapy in critically ill patients.     

Prevalence of hypoxemia in under-five children with pneumonia in an emergency pediatrics hospital in Sudan

Context:

Hypoxemia is a common and potentially lethal complication of acute respiratory infection in children under-five, particularly among those with severe disease.

Aims:

The aim of this study was to determine the prevalence of hypoxemia in under-five Sudanese children with pneumonia.

Settings and Design:

A cross-sectional study conducted in a pediatrics hospital in a developing country.

Subjects and Methods:

Data were collected using structured questionnaire and oxygen saturation was measured using a pulse oximeter. Hypoxemia was defined as arterial blood oxygen saturation <90%.

Results:

Of 150 studied patients, 86 (57.3%) were males and 46 (32%) were in the age group 2 to ≤12 months. Of the total number, 42.7% had hypoxemia (with pulse oximeter oxygen saturation <90%), out of them 36 (56.25%) were in the age group <2 months. Of the hypoxic patients, 30 (46.88%) had severe pneumonia, and 7 (10.94) had very severe pneumonia (P < 0.001).

Conclusions:

The prevalence of hypoxemia was 42.7% among the studied population. There was a significant association between the hypoxemia and small age group and very severe pneumonia. In limited resource settings pulse oximeter can be used to correctly identify hypoxemia in under-five children particularly among those diagnosed clinically as very severe pneumonia.     

Comparison of acute physiology and chronic health evaluation II and acute physiology and chronic health evaluation IV to predict intensive care unit mortality

Context:

Clinical assessment of severity of illness is an essential component of medical practice to predict the outcome of critically ill-patient. Acute Physiology and Chronic Health Evaluation (APACHE) model is one of the widely used scoring systems.

Aims:

This study was designed to evaluate the Performance of APACHE II and IV scoring systems in our Intensive Care Unit (ICU).

Settings and Design:

A prospective study in 6 bedded ICU, including 76 patients all above 15 years.

Subjects and Methods:

APACHE II and APACHE IV scores were calculated based on the worst values in the first 24 h of admission. All enrolled patients were followed, and outcome was recorded as survivors or nonsurvivors.

Statistical Analysis Used:

SPSS version 17.

Results:

The mean APACHE score was significantly higher among nonsurvivors than survivors (P < 0.005). Discrimination for APACHE II and APACHE IV was fair with area under receiver operating characteristic curve of 0.73 and 0.79 respectively. The cut-off point with best Youden index for APACHE II was 17 and for APACHE IV was 85. Above cut-off point, mortality was higher for both models (P < 0.005). Hosmer–Lemeshow Chi-square coefficient test showed better calibration for APACHE II than APACHE IV. A positive correlation was seen between the models with Spearman''s correlation coefficient of 0.748 (P < 0.01).

Conclusions:

Discrimination was better for APACHE IV than APACHE II model however Calibration was better for APACHE II than APACHE IV model in our study. There was good correlation between the two models observed in our study.     

Prevalence of ocular manifestations in systemic sclerosis patients

Introduction

Systemic sclerosis (scleroderma, SSc) is a severe chronic connective tissue disease caused by immune system disorders and changes in the structure and functions of blood vessels, which consequently leads to enhanced tissue fibrosis. The aim of the study was to evaluate changes in the organ of vision in systemic sclerosis patients.

Material and methods

Overall the study involved 27 patients with systemic sclerosis. The control group comprised 27 age- and gender-matched healthy individuals. All the study subjects underwent complete ophthalmological examination that in systemic sclerosis patients additionally involved fluorescein angiography.

Results

Ophthalmological examination revealed higher incidence of the following abnormalities in the study group, compared to the control: symptoms of dry eye syndrome (19 eyes, p < 0.02), astigmatism(in 30 eyes, p < 0.01), posterior subcapsular cataract (10 eyes, p < 0.05), increased intraocular pressure (> 21 mm Hg were observed in 11 eyes, p < 0.002) and vascular abnormalities within fundus in fluorescein angiography (20 eyes).

Conclusions

In patients with systemic sclerosis numerous abnormalities within the vision of organ may be found. Regular ophthalmological examinations are essential among the mentioned group. The examination should be particularly focused on the presence of retinal vascular abnormalities.     

The effects of botulinum toxin type A on improvement and dynamic spastic equinus correction in children with cerebral palsy – preliminary results

Introduction

We evaluated the effects of botulinum toxin type A (BTA) with physical therapy on dynamic foot equinus correction and higher motor functional outcome in children with spastic type of cerebral palsy (CP).

Material and methods

Ankle joint active and passive movement, gastrocnemial muscle spasticity levels (Modified Ashworth Scale (MAS)), and higher motor functional status (Gross Motor Function Classification System (GMFCS) and Gross Motor Function Measure (GMFM) (GMFM-D – standing and GMFM-E – walking) were assessed before treatment and 3, 8, 16 weeks and 6 months after BTA administration in 12 children.

Results

There was a significant improvement of active (initial – (–)13.07 ±5.78; 6 months – (–)10.64 ±4.77; p < 0.001) and passive (initial – 4.21 ±2.29; 6 months – 4.71 ±2.16; p < 0.05) ankle joint foot dorsiflexion. GMFM-D and GMFM-E were significantly higher after 3, 8, 16 weeks (p < 0.001) and GMFM-D after 6 months (p < 0.001).

Conclusions

Botulinum toxin type A administration and physical therapy in patients with spastic CP improves the motion range of dynamic foot equinus after 3 weeks and higher motor functional outcome (standing and walking).     

Neutrophil-to-lymphocyte ratio for the assessment of hospital mortality in patients with acute pulmonary embolism

Introduction

Neutrophil-to-lymphocyte ratio (NLR), which is an essential marker of inflammation, has been shown to be associated with adverse outcomes in various cardiovascular diseases in the literature. In this study we sought to evaluate the association between NLR and prognosis of acute pulmonary embolism (APE).

Material and methods

We retrospectively evaluated blood counts and clinical data of 142 patients with the diagnosis of pulmonary embolism (PE) from Ondokuz Mayis University Hospital between January 2006 and December 2012. The patients were divided into two groups according to NLR: NLR < 4.4 (low NLR group, n = 71) and NLR ≥ 4.4 (high NLR group, n = 71).

Results

Massive embolism (66.2% vs. 36.6%, p < 0.001) and in-hospital mortality (21.1%, 1.4%, p < 0.001) were higher in the high NLR group. In multivariate regression analysis NLR ≥ 5.7, systolic blood pressure (BP) < 90 mm Hg, serum glucose > 126 mg/dl, heart rate > 110 beats/min, and PCO₂ < 35 or > 50 mm Hg were predictors of in-hospital mortality. The optimal NLR cutoff value was 5.7 for mortality in receiver operating characteristic (ROC) analysis. Having an NLR value above 5.7 was found to be associated with a 10.8 times higher mortality rate than an NLR value below 5.7.

Conclusions

In patients presenting with APE, NLR value is an independent predictor of in-hospital mortality and may be used for clinical risk classification.     

Correlation of adrenomedullin with the erythropoietin receptor and microvessel density in hepatocellular carcinoma

Introduction

Uncontrolled angiogenesis plays an essential role in the occurrence, metastasis and malignant progression of hepatocellular carcinoma (HCC). This study aimed to investigate the expression of adrenomedullin (ADM) in human HCC and its correlation with the expression of erythropoietin receptor (EPOR), microvessel density (MVD) and the tumor pathological characteristics.

Material and methods

Fresh tumor tissues were obtained from 30 HCC patients after hepatectomy. Ten cirrhotic and 10 normal liver tissues were included as controls. Expression of ADM and EPOR was determined by real-time PCR. The MVD was determined by counting the number of microvessels.

Results

The MVD and the mRNA levels of ADM and EPOR in cancer tissues were significantly higher than those in the non-cancer tissues (p < 0.05). Expression of ADM was significantly correlated with the MVD and EPOR (r = 0.68 and 0.74, p < 0.01). Adrenomedullin and EPOR mRNA levels in HCC tissues were correlated with capsule invasion, pathological differentiation and tumor metastasis (p < 0.05).

Conclusions

Our findings suggest that ADM and EPOR may serve as new regulatory factors involved in angiogenesis of HCC and represent novel targets for the treatment of HCC.     

Ondansetron-droperidol combination vs. ondansetron or droperidol monotherapy in the prevention of postoperative nausea and vomiting

Introduction

Laparoscopic cholecystectomy is associated with a high incidence of postoperative nausea and vomiting. In this study we investigated comparatively the efficacy of combination therapy with ondansetron plus droperidol versus monotherapy with each agent alone in preventing postoperative nausea and vomiting following elective laparoscopic cholecystectomy.

Material and methods

One hundred twenty-seven patients who underwent elective laparoscopic cholecystectomy under general anesthesia were included in the study, and assigned to one of the following three groups according to the antiemetic drug given intravenously at the end of the surgery: droperidol 1.25 mg in group D, ondansetron 4 mg in group O, and a combination of droperidol and ondansetron at the doses mentioned above in group D + O. Incidence of postoperative nausea and vomiting, and doses of given rescue antiemetics were recorded during the first postoperative day. The total drug cost per patient spent for postoperative nausea and vomiting management (including prophylactic antiemetics plus rescue postoperative antiemetics) was calculated.

Results

Combination therapy significantly reduced postoperative nausea and vomiting at 30 min, 3 h and 6 h after surgery compared with group D (p < 0.01 for all time points) and O (p < 0.01 at 30 min, p < 0.05 at 3 h) and required less rescue antiemetic treatment (p < 0.01). Total antiemetic cost analyses revealed no significant differences among the three groups (p > 0.05).

Conclusions

Pretreatment with ondansetron plus droperidol is more effective than monotherapy in preventing postoperative nausea and vomiting following laparoscopic cholecystectomy, without increasing the cost comparatively.